The objective of this proposed research is to study the substrate specificity and catalytic mechanism of the antilymphosarcoma enzyme, L- asparaginase. The enzymology of the E. coli and Erwinia enzymes will be compared in order to evaluate the relative potential of the two enzymes in chemotherapy. Second, in order to better understand the molecular origin of side effects from L-asparaginase therapy, we will investigate the results of asparagine and/or glutamine starvation in normal tissue. Finally, we will prepare and characterize modified L-asparaginase in an attempt to produce enzyme with diminished side effects and expanded utility or efficiency in chemotherapy.